European Journal of Pharmaceutical Sciences最新文献

{"title":"Thermosensitive in situ gels for ocular drug delivery: Advances in polymer-based formulations","authors":"Raghad Alsheikh ,&nbsp;Dániel Nemes ,&nbsp;Pálma Fehér ,&nbsp;Zoltán Ujhelyi ,&nbsp;Ádám Haimhoffer ,&nbsp;Ádám Papp ,&nbsp;Ildikó Bácskay","doi":"10.1016/j.ejps.2026.107439","DOIUrl":"10.1016/j.ejps.2026.107439","url":null,"abstract":"<div><div>Ocular drug delivery presents significant challenges due to the unique anatomical and physiological barriers of the human eye, with the rapid precorneal elimination, limiting the bioavailability of conventional eye drops. Thermosensitive in situ gels have emerged as a promising delivery system to overcome these limitations by undergoing a reversible sol-to-gel transition upon contact with ocular surface temperature, which facilitates ease of administration as a liquid and subsequent transformation into a gel, thereby enhancing precorneal residence time, prolonging the drug release, and improving therapeutic efficacy. This review provides a comprehensive overview of thermos-responsive polymer-based ocular delivery systems, with a specific focus on poloxamers, poly(N-isopropylacrylamide), and cellulose derivatives. Particular attention is given to the physicochemical mechanisms of thermogelation, such as poloxamer micellization and micelle packing, as well as the role of auxiliary polymers in enhancing mucoadhesion, mechanical strength, and gel retention. Additionally, the review synthesizes findings from multiple experimental studies to highlight the critical formulation parameters essential for developing effective in situ gels, including sol–gel transition temperature and time, clarity, rheological behavior, gelling capacity, isotonicity, and ocular biocompatibility. By selecting an optimized thermosensitive in situ gel formulation with suitable characteristics, it becomes possible to develop effective delivery systems targeting both the anterior and posterior segments of the eye.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107439"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of a novel anti-TSLP bispecific antibody (GR2002) in healthy Chinese adults: A randomized, placebo-controlled phase 1 trial","authors":"Rui Ding ,&nbsp;Fan Huang ,&nbsp;Ziyan Ding ,&nbsp;Yanting Li ,&nbsp;Qun Gu ,&nbsp;Fang Men ,&nbsp;Chongyou Lee ,&nbsp;Jiaojiao Zhang ,&nbsp;Wenyan Zhao ,&nbsp;Qian Wang ,&nbsp;Yian Liu ,&nbsp;Shuang Li ,&nbsp;Qingshan Zheng ,&nbsp;Haifeng Song ,&nbsp;Liming Chen ,&nbsp;Wei Wang ,&nbsp;Suping Niu ,&nbsp;Yi Fang","doi":"10.1016/j.ejps.2026.107432","DOIUrl":"10.1016/j.ejps.2026.107432","url":null,"abstract":"<div><h3>Background</h3><div>GR2002 is a novel bispecific antibody targeting dual epitopes on thymic stromal lymphopoietin (TSLP). We aimed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of GR2002 in healthy Chinese adults.</div></div><div><h3>Methods</h3><div>In this randomized, double-blind, placebo-controlled, dose-escalation, phase 1 trial of GR2002, healthy adults were enrolled and assigned to one of five dose cohorts. Within each cohort, participants were randomized (4:1) to receive a single subcutaneous dose of GR2002 (35, 70, 140, 280, or 420 mg) or placebo and were followed for 85 days. The primary endpoints included safety and tolerability. Secondary endpoints comprised PK, PD, and immunogenicity.</div></div><div><h3>Results</h3><div>Fifty eligible subjects were enrolled and randomized to receive either GR2002 (<em>n</em> = 40) or placebo (<em>n</em> = 10). A total of 92 treatment-emergent adverse events (TEAEs) were reported, with comparable incidence between the GR2002 and placebo groups. TEAEs were generally mild to moderate in severity and did not exhibit dose dependency. The most common treatment-related adverse event was upper respiratory tract infection, occurring in 7/40 (17.5%) participants in the GR2002 group and 2/10 (20%) in the placebo group. GR2002 displayed linear PK across the dose range tested, with a mean half-life ranging from 26.0 to 58.9 days. Dose-dependent reductions in serum TSLP levels from baseline were observed in the 140–420 mg dose groups. Anti-drug antibodies were detected in six subjects (15%) following GR2002 administration.</div></div><div><h3>Conclusions</h3><div>Single-dose subcutaneous administration of GR2002 demonstrated favorable safety and tolerability, linear PK, and low immunogenicity. These findings warrant the subsequent clinical development of GR2002.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107432"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and evaluation of dual-functional aptamer-peptide conjugates as a platform for targeted cancer therapy","authors":"Simona Marzano ,&nbsp;Maria Grazia Ferraro ,&nbsp;Nicola Grasso ,&nbsp;Rossella Buono ,&nbsp;Valentina Arciuolo ,&nbsp;Federica Iazzetti ,&nbsp;Marialuisa Piccolo ,&nbsp;Assunta Passarelli ,&nbsp;Federica D’Aria ,&nbsp;Francesco Merlino ,&nbsp;Paolo Grieco ,&nbsp;Antonio Randazzo ,&nbsp;Bruno Pagano ,&nbsp;Carlo Irace ,&nbsp;Jussara Amato","doi":"10.1016/j.ejps.2026.107428","DOIUrl":"10.1016/j.ejps.2026.107428","url":null,"abstract":"<div><div>AS1411 is a G-rich DNA aptamer that exhibits intrinsic antitumor activity through selective binding to nucleolin, a protein overexpressed in many cancers. Beyond its cytotoxic effects, AS1411 can also serve as an effective targeting ligand for the delivery of therapeutics with poor cellular uptake, including peptide-based drugs. One such candidate is the pro-apoptotic peptide KLA, which selectively disrupts mitochondrial membranes and induces apoptosis upon internalization. In this study, AS1411-KLA conjugates were designed and synthesized using strain-promoted azide-alkyne cycloaddition chemistry, incorporating protease-cleavable peptide linkers to enable intracellular release of both the aptamer and peptide as independent active units. Circular dichroism analysis showed that, in all constructs, the AS1411 domain preserved the characteristic G-quadruplex structural features, while surface plasmon resonance experiments revealed that all conjugates retained nucleolin binding. The biological activity of the conjugates was evaluated in MCF-7 breast cancer cells and in non-tumorigenic MCF-10A cells, and compared with that of the individual aptamer and peptide. One conjugate displayed an enhanced antiproliferative effect compared to the unconjugated components, underscoring the therapeutic potential of this modular design. Overall, this work demonstrates the potential of aptamer-peptide conjugates as a promising strategy for next-generation targeted cancer therapeutics, combining targeted delivery with synergistic therapeutic effects.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107428"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145932985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the Morphology of Small Multilamellar Lipid Nanoparticles (SMLPs) made by In-Vial Homogenization","authors":"Sevda Akcesme ,&nbsp;Stefanie Schmager ,&nbsp;Yassir Al-Tikriti ,&nbsp;Lars Gedda ,&nbsp;Magnus Bergström ,&nbsp;Katarina Edwards ,&nbsp;Heiko Heerklotz ,&nbsp;Ulrich Massing","doi":"10.1016/j.ejps.2026.107451","DOIUrl":"10.1016/j.ejps.2026.107451","url":null,"abstract":"<div><div>Previous research shows that thermosensitive small multilamellar lipid nanoparticles (tSMLPs) offer promising features for temperature-triggered cytostatic drug delivery, remaining completely stable at body temperature (37°C) and releasing their payload under mild hyperthermia conditions (42°C). A distinguishing characteristic of tSMLPs is their unique particle morphology - multiple tightly packed bilayers with progressively decreasing intermembrane spacing toward the particle core. In this study, we shift the focus from their thermosensitivity to an in-depth exploration of the particle’s morphology. Using in-vial homogenization by dual centrifugation (DC) at very high lipid concentrations (60%), we prepare SMLPs composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol (DPPG₂). A systematic screening of DPPC/DPPG₂ 100-x/x (mol/mol) from x = 0 to 100 enabled the formation of SMLPs with sizes below 200 nm, narrow size distribution and well-distinguishable morphologies. These lipid nanoparticles also demonstrated the capacity to entrap hydrophilic compounds, despite their multilamellar structure and thus limited interlamellar aqueous space. We propose that specific headgroup interactions between DPPC and DPPG₂ underlie the observed water influx upon dilution of the initially formed vesicular phospholipid gels (VPGs) during in-vial homogenization by DC. With a combination of biophysical techniques (DLS, Time-resolved fluorescence, SAXS and WAXS) and morphological analysis (cryo-EM), we present a hypothesis to explain the evolving SMLP morphology as a function of increasing DPPG₂ content in the phospholipid blend.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"218 ","pages":"Article 107451"},"PeriodicalIF":4.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linagliptin attenuates kidney cancer in rats via AMPK activation and suppression of YAP/TAZ/HIF-1α signaling","authors":"Tahani Saeedi ,&nbsp;Mohannad Almikhlafi ,&nbsp;Hossein M Elbadawy ,&nbsp;Muayad S Albadrani ,&nbsp;Rehab F Abdel-Rahman ,&nbsp;Gihan F. Asaad ,&nbsp;Fatma A Ibrahim ,&nbsp;Aya A. Shokry ,&nbsp;Tuba Esatbeyoglu ,&nbsp;Sherif M. Afifi ,&nbsp;Hany M Fayed ,&nbsp;Marawan A. Elbaset","doi":"10.1016/j.ejps.2025.107393","DOIUrl":"10.1016/j.ejps.2025.107393","url":null,"abstract":"<div><div>This study investigated the renoprotective action of linagliptin compared to doxorubicin against thioacetamide (TAA) and diethyl nitrosamine (DEN)-induced renocarcinogenesis in a rat model. Male Wistar rats were divided into control, renocarcinogenesis (RCC), doxorubicin group (7.5 mg/kg, i.p., once weekly), and linagliptin (Lina) groups (3 and 6 mg/kg/day, p.o.). The experiment included renal function parameters, oxidative stress markers, and predominant molecular pathways involved in renal pathogenesis. The RCC model significantly impaired renal function, as reflected in elevated serum levels of urea and creatinine. It also resulted in elevated oxidative stress, as reflected in increased malondialdehyde (MDA) content and decreased glutathione and superoxide dismutase (GSH and SOD) activities. The model disrupted several molecular pathways, including the AMP-activated protein kinase (AMPK) pathway, and enhanced oncogenic and inflammatory markers such as Yes-associated protein/ Transcriptional coactivator with PDZ-binding motif/ Hypoxia-inducible factor 1-alpha (YAP/TAZ/ HIF-1α), nuclear factor erythroid 2-related factor 2/ Sirtuin 1(Nrf2/SIRT1), and signal transducer and activator of transcription 3 (STAT3). Treatment with linagliptin, particularly the high dose (6 mg/kg/day), was found to be superior to doxorubicin treatment in terms of correction of renal function and markers of oxidative stress. Linagliptin effectively regulated the AMPK pathway, reduced markers of inflammation, restored the expression of genes with key roles in renal protection, reduced proliferating Cell Nuclear Antigen (PCNA), and elevated Caspase-3. The high dose of linagliptin exhibited superior results in most of the parameters, which approached control levels more than those with the lower dose and doxorubicin. These findings demonstrate that linagliptin, especially at 6 mg/kg/day, exhibits significant renoprotective activities through multifarious mechanisms involving antioxidant action and regulation of key molecular pathways. The present study presents evidence for the potential therapeutic application of linagliptin in renal manifestations of renocarcinogenesis.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107393"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “Intratracheal instillation of chitosan-coated formononetin-loaded porous microspheres prolongs lung retention and improves the treatment” [European Journal of Pharmaceutical Sciences. 2025 Dec 1;215:107347]","authors":"Conglu Zhao ,&nbsp;Liyuan Ji ,&nbsp;Xiaoting Wang ,&nbsp;Jia Zhang ,&nbsp;Xiang Xu ,&nbsp;Xiaoting Zhang ,&nbsp;Yanjie Ding ,&nbsp;Keran Li ,&nbsp;Chaoyue Zheng ,&nbsp;Kaijun Qiu ,&nbsp;Jing Yan ,&nbsp;Songtao Gu ,&nbsp;Honggang Zhou ,&nbsp;Cheng Yang ,&nbsp;Hongli Li ,&nbsp;Xiaoting Gu ,&nbsp;Xiaoyu Ai","doi":"10.1016/j.ejps.2025.107412","DOIUrl":"10.1016/j.ejps.2025.107412","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107412"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing therapeutics with targeted formulations of hydrogen sulphide donors","authors":"Mandeep Kaur Marwah ,&nbsp;Lissette Sanchez-Aranguren ,&nbsp;Hala Shokr ,&nbsp;Mohamad Anas Al Tahan ,&nbsp;Keqing Wang ,&nbsp;Shakil Ahmad","doi":"10.1016/j.ejps.2025.107408","DOIUrl":"10.1016/j.ejps.2025.107408","url":null,"abstract":"<div><div>Hydrogen sulphide (H₂S), is a well described essential physiological molecule that is finely balanced to maintain cellular functions. Considering its important biological roles, H₂S has promising therapeutic potential resulting in the development of many H₂S donors. Such donors have proved to have therapeutic benefit in cognitive pathways, inflammation, reproduction, and the regulation of blood pressure. However, controlled delivery and targeted administration of this reactive and hazardous gas are necessary yet challenging due to its rapid diffusivity, and toxicity at high doses. Drug delivery systems are vital for the effective administration of many active pharmaceutical excipients, and H₂S donors stands to benefit significantly from the tuneable physical, chemical, and pharmacokinetic properties of various formulation systems. To date, few studies have focused on the formulation and delivery aspects of H₂S and its donors. Instead, H₂S usually is administered either by inhalation or via site-specific injections of donor solution. Whilst therapeutic benefit has been observed following such administration, these are not patient friendly solutions. This review focuses on highlighting the advances in H₂S donor formulations and their ability in sustaining the release of H₂S as well as improving drug targeting.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107408"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic profile of dexamethasone in urine and plasma after single and multiple oral administration: Relevance to doping controls","authors":"Sergi Coll ,&nbsp;Claudia Bressan ,&nbsp;Núria Monfort ,&nbsp;Ana Aldea-Perona ,&nbsp;Marcel·lí Carbó ,&nbsp;Rosa Ventura","doi":"10.1016/j.ejps.2025.107405","DOIUrl":"10.1016/j.ejps.2025.107405","url":null,"abstract":"<div><div>Dexamethasone (DEX) is prohibited in sports competitions when administered by all injectable, oral or rectal routes, and is permitted at all times when administered by all other routes. The present work aimed to assess the urinary excretion profile of DEX after single and multiple oral administrations to verify the suitability of the new minimum reporting level (MRL) of 60 ng/mL established by the World Anti-Doping Agency to distinguish allowed and prohibited administrations. Moreover, the minimum washout period of three days established for out-of-competition treatments with oral glucocorticoids will be evaluated.</div><div>DEX was administered to healthy volunteers using two different oral treatments: single administration (4 mg, <em>n</em> = 8 male volunteers) and multiple administrations (2 mg/12 h for 5 days, <em>n</em> = 8 male volunteers). Urine and plasma samples collected before and after administration were analysed using liquid chromatography-tandem mass spectrometry. DEX and 6β‑hydroxy-DEX, were the predominant compounds detected in urine, with peak urinary excretion observed within the first 4 h post-dose. DEX concentrations exceeded the new MRL mainly within 12 h after a single dose, with one volunteer showing levels above this threshold up to 24–36 h. In the multiple-dose study, most of the DEX concentrations remained above 60 ng/mL after the second dose and throughout the dosing period and declined quickly after the final dose. Plasma DEX kinetics was defined by an open bicompartmental model with a first order oral absorption. DEX was detectable up to 48 h post-administration. In the multiple dose study, the steady-state concentrations were reached soon after the first dose, and DEX showed no evidence of accumulation. CORT levels decreased rapidly after both single and multiple administrations due to suppression of the hypothalamic-pituitary-adrenal axis. Recovery times varied among volunteers.</div><div>The MRL of 60 ng/mL proved appropriate for distinguishing permitted from prohibited use with a 3-day washout, though further studies on non-systemic routes are recommended to refine sensitivity.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107405"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Update on clinical trials of intra-articular disease-modifying osteoarthritis drugs inducing cartilage regeneration","authors":"Luca Morici ,&nbsp;Ines Nikolic","doi":"10.1016/j.ejps.2025.107403","DOIUrl":"10.1016/j.ejps.2025.107403","url":null,"abstract":"<div><div>Osteoarthritis is the most common degenerative joint disease affecting millions of people in the world and leading to disability. Currently, the only available treatments on the market are symptomatic therapies for pain and inflammation. There are no intra-articular drugs that can restore the cartilage matrix, also known as disease-modifying osteoarthritis drugs (DMOADs). This review focuses on all clinical trials of pro-anabolic DMOADs, which stimulate the regeneration of the cartilage matrix by inducing the differentiation of mesenchymal progenitors into chondrocytes, a process known as chondrogenesis. This review also discussed some pathways of chondrocytes, which boost the transcription of genes involved in the production of extracellular matrix components. Finally, the review also covers some implants in the commercial and clinical phases for cartilage repair.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107403"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,3,5-Triazine-benzenesulfonamide hybrids: are they cytotoxic?","authors":"Mária Bodnár Mikulová ,&nbsp;Jana Hricovíniová ,&nbsp;Michal Hanko ,&nbsp;Gabriela Greifová","doi":"10.1016/j.ejps.2025.107416","DOIUrl":"10.1016/j.ejps.2025.107416","url":null,"abstract":"<div><div>In contemporary pharmaceutical research, cytotoxicity assays constitute an indispensable tool in the systematic evaluation of drug candidates. The identification of cytotoxic effects at early stages of development is critical, as it allows for the elimination of compounds with unfavourable toxicological properties prior to their advancement into preclinical and clinical testing. Despite the essential role of cytotoxicity studies, the relationship between chemical structure and cytotoxic outcome remains insufficiently defined for many classes of compounds. In this context, 1,3,5-triazine derivatives have emerged as a particularly promising scaffold due to their broad spectrum of biological activities, with notable emphasis on anticancer potential. However, the absence of a comprehensive structure–cytotoxicity correlation highlights the need for systematic evaluation and consolidation of findings. In this review, we provide an overview of triazine-benzenesulfonamide hybrid molecules, including their synthesis and purification procedures, as well as their biological activity and cytotoxicity. The novel strategies in new candidate drug development and structure modifications related to their effects on investigated protein and/or non-protein targets, as well as various cell lines, are included to demonstrate a relationship between structure and antiproliferative activity, as well as cytotoxicity. Moreover, the literature reveals substantial variability in the methods used to assess antiproliferative and cytotoxic activity, which hinders comparisons and the interpretation of structure–activity relationships. Adoption of a standardized framework—particularly consistent reporting of IC₅₀ values—would improve reproducibility, facilitate meaningful cross-study comparisons, and provide a stronger foundation for linking molecular design with biological response. Ultimately, such standardisation may advance drug discovery and support the rational modification of chemical structures to enhance therapeutic potential.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107416"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}